Chitosan, as a biocompatible and biodegradable polysaccharide, has attracted considerable attention from various industries. VandeVord, P. J., Matthew, H. W. T., DeSilva, S. P., Mayton, L., Wu, B., Wooley, P. H.; J. Biomed. Mater. Res. 2002, 59, 585-590. Many attempts have been made to modify the molecular structure of chitosan in order to introduce certain properties into the molecule. Yu et al., Biomacromolecules; 8(5); 1425-1435 (2007).
However, chemical reactions with chitosan are usually carried out under harsh and heterogeneous conditions (i.e., higher temperature and longer reaction time compared with the corresponding homogeneous conditions) and often involve multi-step protection and deprotection protocols due to the poor solubility of the molecule in common organic solvents. A typical approach is to 1) react chitosan directly with a cyclic anhydride in a solution such as dimethylformamide and water at a temperature of 100° C.-120° C. to obtain a first intermediate; 2) react the first intermediate with a pyridine and reactant such as triphenylchloromethane at 85° C.-105° C. to obtain a second intermediate; and 3) react the second intermediate with further reactants such as hydrazine monohydrate and water at a temperature of 100° C.-120° C. to obtain a final product. The reaction is exemplified as follows:

However, the final products resulting from these type of reactions have a number of drawbacks Holappa et al., Macromolecules, 37, 2784-2789 (2004). For example, the final products exhibit a low degree of substitution (low modification level due to low reaction activity) and/or an uncontrollable (random) substitution of the functional groups present in chitosan.
The inventors of the present application have discovered an efficient manner for producing organo-rouble chitosan salt under mild conditions. The organo-soluble chitosan salt in turn can be used to produce a novel chitosan derivative.